Pacific Biosciences Research Center, University of Hawaii, Honolulu, HI 96822, USA.
Behav Brain Res. 2011 Mar 1;217(2):302-8. doi: 10.1016/j.bbr.2010.10.033. Epub 2010 Nov 3.
The BTBR T+ tf/J (BTBR) inbred mouse strain displays a low sociability phenotype relevant to the first diagnostic symptom of autism, deficits in reciprocal social interactions. Previous studies have shown that BTBR mice exhibit reduced social approach, juvenile play, and interactive behaviors. The present study evaluated the behavior of the BTBR and C57BL/6J (B6) strains in social proximity. Subjects were closely confined and tested in four experimental conditions: same strain male pairs (Experiment 1); different strain male pairs (Experiment 2); same strain male pairs and female pairs (Experiment 3); same strain male pairs treated with an anxiolytic (Experiment 4). Results showed that BTBR mice displayed decreased nose tip-to-nose tip, nose-to-head and upright behaviors and increased nose-to-anogenital, crawl under and crawl over behaviors. These results demonstrated avoidance of reciprocal frontal orientations in the BTBR, providing a parallel to gaze aversion, a fundamental predictor of autism. For comparative purposes, Experiment 3 assessed male and female mice in a three-chamber social approach test and in the social proximity test. Results from the three-chamber test showed that male B6 and female BTBR displayed a preference for the sex and strain matched conspecific stimulus, while female B6 and male BTBR did not. Although there was no significant interaction between sex and strain in the social proximity test, a significant main effect of sex indicated that female mice displayed higher levels of nose tip-to-nose tip contacts and lower levels of anogenital investigation (nose-to-anogenital) in comparison to male mice, all together suggesting different motivations for sociability in males and females. Systemic administration of the anxiolytic, diazepam, decreased the frequency of two behaviors associated with anxiety and defensiveness, upright and jump escape, as well as crawl under behavior. This result suggests that crawl under behavior, observed at high levels in BTBR mice, is elicited by the aversiveness of social proximity, and possibly serves to avoid reciprocal frontal orientations with other mice.
BTBR T+ tf/J（BTBR）近交系小鼠表现出与自闭症第一个诊断症状相关的社交能力低下表型，即互惠社会互动缺陷。先前的研究表明，BTBR 小鼠表现出社交接近、幼年期玩耍和互动行为减少。本研究评估了 BTBR 和 C57BL/6J（B6）品系在社交接近中的行为。在四个实验条件下，将受试对象紧密限制并进行测试：同品系雄性对（实验 1）；不同品系雄性对（实验 2）；同品系雄性对和雌性对（实验 3）；同品系雄性对接受抗焦虑药治疗（实验 4）。结果表明，BTBR 小鼠的鼻尖对鼻尖、鼻尖对头部和直立行为减少，而鼻对肛门生殖器、爬行下和爬行上行为增加。这些结果表明，BTBR 中存在回避互惠正面定向的行为，这与自闭症的一个基本预测指标——目光回避行为相似。为了进行比较，实验 3 在三箱社交接近测试和社交接近测试中评估了雄性和雌性小鼠。三箱测试的结果表明，雄性 B6 和雌性 BTBR 对性和品系匹配的同种刺激表现出偏好，而雌性 B6 和雄性 BTBR 则没有。尽管在社交接近测试中性别和品系之间没有显著的相互作用，但性别存在显著的主效应，表明雌性小鼠的鼻尖对鼻尖接触次数较高，肛门生殖器调查（鼻对肛门生殖器）次数较低，这表明雄性和雌性的社交动机不同。全身性给予抗焦虑药地西泮可降低与焦虑和防御性相关的两种行为（直立和跳跃逃避）以及爬行下行为的频率。这一结果表明，BTBR 小鼠高水平表现出的爬行下行为是由社交接近的厌恶引起的，并且可能用于避免与其他小鼠的互惠正面定向。
